Metabolism of glycine in primary astroglial cells: synthesis of creatine, serine, and glutathione.
The metabolism of [2-13C]glycine in astroglia-rich primary cultures obtained from brains of neonatal Wistar rats was investigated using 13C NMR spectroscopy. After a 24-h incubation of the cells in a medium containing glucose, glutamate, cysteine, and [2-13C]glycine, cell extracts and incubation media were analyzed for 13C-labeled compounds. Labeled creatine, serine, and glutathione were identified in the cell extracts. If arginine and methionine were present during the incubation with [2-13C]glycine, the amount of de novo synthesized [2-13C]creatine was two-fold increased, and in addition, 13C-labeled guanidinoacetate was found in cell extracts and in the media after 24 h of incubation. A major part of the [2-13C]glycine was utilized for the synthesis of glutathione in astroglial cells. 13C-labeled glutathione was found in the cell extracts as well as in the incubation medium. The presence of newly synthesized [2-13C] serine, [3-13C]serine, and [2,3-13C]serine in the cell extracts and the incubation medium proves the capability of astroglial cells to synthesize serine out of glycine and to release serine. Therefore, astroglial cells are able to utilize glycine as a precursor for the synthesis of creatine and serine. This proves that at least one cell type of the brain is able to synthesize creatine. In addition, guanidinoacetate, the intermediate of creatine synthesis, is released by astrocytes and may be used for creatine synthesis by other cells, i.e., neurons.
Dringen
R
R
Physiologisch-chemisches Institut der Universität, Tübingen, Germany.
Verleysdonk
S
S
Hamprecht
B
B
Willker
W
W
Leibfritz
D
D
Brand
A
A
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D002478:Cells, Cultured; D003401:Creatine / Q000096:biosynthesis*; D005978:Glutathione / Q000096:biosynthesis*; D005998:Glycine / Q000378:metabolism*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000096:biosynthesis*
D002247:Carbon Isotopes; D012694:Serine; D001120:Arginine; D008715:Methionine; D005978:Glutathione; D003401:Creatine; D005998:Glycine